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This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons (PAHs) and their derivatives in one Chinese petroleum refinery facility. It was found that, following with high concentrations of 16 EPA PAHs (∑Parent-PAHs) in smelting subarea of studied petroleum refinery facility, total derivatives of PAHs [named as XPAHs, including nitro PAHs (NPAHs), chlorinated PAHs (Cl-PAHs), and brominated PAHs (Br-PAHs)] in gas (mean= 1.57 × 104 ng/m3), total suspended particulate (TSP) (mean= 4.33 × 103 ng/m3) and soil (mean= 4.37 × 103 ng/g) in this subarea had 1.76-6.19 times higher levels than those from other subareas of this facility, surrounding residential areas and reference areas, indicating that petroleum refining processes would lead apparent derivation of PAHs. Especially, compared with those in residential and reference areas, gas samples in the petrochemical areas had higher ∑NPAH/∑PAHs (mean=2.18), but lower ∑Cl-PAH/∑PAHs (mean=1.43 × 10-1) and ∑Br-PAH/∑PAHs ratios (mean=7.49 × 10-2), indicating the richer nitrification of PAHs than chlorination during petrochemical process. The occupational exposure to PAHs and XPAHs in this petroleum refinery facility were 24-343 times higher than non-occupational exposure, and the ILCR (1.04 × 10-4) for petrochemical workers was considered to be potential high risk. Furthermore, one expanded high-resolution screening through GC Orbitrap/MS was performed for soils from petrochemical area, and another 35 PAHs were found, including alkyl-PAHs, phenyl-PAHs and other species, indicating that profiles and risks of PAHs analogs in petrochemical areas deserve further expanded investigation.
Subject(s)
Environmental Monitoring , Petroleum , Polycyclic Aromatic Hydrocarbons , Polycyclic Aromatic Hydrocarbons/analysis , China , Petroleum/analysis , Humans , Oil and Gas Industry , Environmental Exposure/analysis , Air Pollutants/analysis , Risk AssessmentABSTRACT
Smart packaging material capable of real-time monitoring of food freshness is essential for ensuring food safe. At present, colorimetric ammonia-sensing smart film often possesses issues with complicated production, high cost, and inferior long-term colour stability. Herein, Zinccopper bimetallic organic framework (ZnCu-BTC, BTC = 1,3,5-benzenetricarboxylate acid) nanorods with colorimetric ammonia-responsiveness were synthesized by adopting facile aqueous solution method, which were then explored as nano inclusions in potato starch/polyvinyl alcohol (PS/PVA) composite film towards developing high-performance smart packaging material. The results demonstrated that the introduction of ZnCu-BTC nanorods within PS/PVA brought about remarkable improvement in blend compatibility, accompanied by a boost in tensile strength to 47.2 MPa, as well as enhanced ultraviolet (UV) blocking efficacy (over 95.0 %). Additionally, the barrier properties of PS/PVA film against water vapor and oxygen were fortified due to the addition of ZnCu-BTC. More importantly, the developed PS/PVA/ZnCu-BTC nanocomposite film displayed satisfactory antibacterial activity (over 99 %) against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), favorable colorimetric ammonia-sensing ability, and long-term colour stability. The ZnCu-BTC incorporated PS/PVA nanocomposite film could grant real-time detection of prawn freshness decline via remarkable colour change, indicating vast promise for smart food packaging applications.
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Tumor spread through air spaces (STAS) is a distinctive metastatic pattern affecting prognosis in lung adenocarcinoma (LUAD) patients. Several challenges are associated with STAS detection, including misdetection, low interobserver agreement, and lack of quantitative analysis. In this research, a total of 489 digital whole slide images (WSIs) were collected. The deep learning-based STAS detection model, named STASNet, was constructed to calculate semi-quantitative parameters associated with STAS density and distance. STASNet demonstrated an accuracy of 0.93 for STAS detection at the tiles level and had an AUC of 0.72-0.78 for determining the STAS status at the WSI level. Among the semi-quantitative parameters, T10S, combined with the spatial location information, significantly stratified stage I LUAD patients on disease-free survival. Additionally, STASNet was deployed into a real-time pathological diagnostic environment, which boosted the STAS detection rate and led to the identification of three easily misidentified types of occult STAS.
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In this editorial we comment on the article by Huffaker et al published in a recent issue of the World Journal of Clinical Cases. We focus on cardiac tumors linked to genetic syndromes and the differential diagnosis of cardiac masses. As cardiomyocytes lack the ability to actively divide, primary cardiac tumors are extremely rare across all ethnicities and age groups. Once they occur, these tumors are often associated with genetic mutations and, occasionally, genetic syndromes. This underscores the importance of considering genetic mutations and syndromes when encountering these cases. The more common growths in the heart are thrombi and vegetations, which can mimic tumors, further making the differential diagnosis challenging. Among the imaging techniques, contrast-enhanced cardiac magnetic resonance imaging has the highest sensitivity for differential diagnosis. To aid in the differential diagnosis of cardiac masses, especially thrombi, appropriate utilization of biomarkers (i.e. D-dimer level) may provide pivotal clinical implications. Employing a multidisciplinary approach that integrates personal history, epidemiological insights, imaging findings, genetic markers, and biomarkers is therefore critical in the diagnostic process of cardiac masses.
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The aim of the study is to analyze ventricular-vascular properties with different ventricular-arterial coupling (VAC) ratio in the preeclamptic women. Seventy-seven pregnant women with preeclampsia and eighty-nine with normal pregnancy were performed echocardiography. VAC was defined as the ratio between aortic elastance (Ea) and left ventricular (LV) end-systolic elastance (Ees). Using the VAC value of 0.8 as the cut-off near uncoupling, the preeclampsia cases were divided into two subgroups: VAC ratio ≥ 0.8 and <0.8. Cardiac structure and function, VAC properties, as well as four components of the LV pressure-strain loop, including global myocardial work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were determined. The preeclampsia with VAC ≥ 0.8 had an enlarger indexed ventricular volume and a thicker relative ventricular wall than the VAC < 0.8. The Ees significantly increased in the subgroup with VAC < 0.8 and decreased in the VAC ≥ 0.8, while the Ea increased in both of them. The preeclampsia with VAC ≥ 0.8 showed an obvious augmentation in GWI, GCW and GWE, along with a similar GWW compared to those with VAC < 0.8. There were variable relationships between the LV pressure-strain components and VAC properties. Thus, the preeclampsia with VAC ≥ 0.8 undergoes a more adverse remodeling and a greater impact on cardiac contractility. The increased stiffness of the heart and arterial system, and increased resistance of peripheral vessels net lead to the deteriorative ventricular efficiency with elevated myocardial oxygen consumption during a preeclampsia pregnancy.
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PURPOSE: To investigate the influence of transarterial embolization (TAE) on programmed cell death-ligand 1(PD-L1) expression and CD8+T tumour infiltrative lymphocyte cytotoxicity in the Sprague-Dawley (SD) rat model of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: An orthotopic HCC model was established in twenty SD rats treated with TAE (lipiodol, n = 10) or sham (normal saline, n = 10) using homologous N1S1 hepatoma cells. Rats were euthanized 1 week after embolization. Flow cytometry was used to assess the proportion of CD4+T, CD8+T and programmed cell death-1+(PD-1+) CD8+T lymphocytes in the spleens and tumours. Distribution of CD8+T, granzyme-B+CD8+T lymphocytes and PD-L1+ cells was assessed by immunohistochemistry (IHC) or multiplex IHC. p value < 0.05 was considered statistically significant. RESULTS: The CD4/CD8 ratio and PD-1+CD8+ T lymphocytes exhibited higher values in TAE-treated tumours compared to sham-treated tumours (p = 0.021 and p = 0.071, respectively). Conversely, the number of CD8+T lymphocytes was decreased in TAE-treated tumours (p = 0.043), especially in the central region (p = 0.045). However, more CD8+T lymphocytes were found infiltrating the marginal region than central region in TAE-treated tumours (p = 0.046). The proportion of granzyme-B+CD8+T lymphocytes and the PD-L1 positive areas was elevated in tumours that treated with TAE (p all < 0.05). There was a negative correlation between PD-L1 expression and the number of infiltration of CD8+ T lymphocytes (p = 0.036). CONCLUSIONS: Immune cells are distributed unevenly in the tumours after TAE. The intrinsic induction state of the tumour after embolization may be insufficient to elicit a maximal response to PD-1/PD-L1 inhibitors.
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A series of progress has been made in the field of antimicrobial use of nanozymes due to their superior stability and decreased susceptibility to drug resistance. However, catalytically generated reactive oxygen species (ROS) are insufficient for coping with multidrug-resistant organisms (MDROs) in complex wound environments due to their low targeting ability and insufficient catalytic activity. To address this problem, chemically stable copper-gallic acid-vancomycin (CuGA-VAN) nanoneedles were successfully constructed by a simple approach for targeting bacteria; these nanoneedles exhibit OXD-like and GSH-px-like dual enzyme activities to produce ROS and induce bacterial cuproptosis-like death, thereby eliminating MDRO infections. The results of in vitro experiments showed that the free carboxylic acid of GA could react with the free ammonia of teichoic acid in the methicillin-resistant Staphylococcus aureus (MRSA) cell wall skeleton. Thus, CuGA-VAN nanoneedles can rapidly "capture" MRSA in liquid environments, releasing ROS, VAN and Cu2+ on bacterial surfaces to break down the MRSA barrier, destroying the biofilm. In addition, CuGA-VAN effectively promoted wound repair cell proliferation and angiogenesis to facilitate wound healing while ensuring biosafety. According to transcriptome sequencing, highly internalized Cu2+ causes copper overload toxicity; downregulates genes related to the bacterial glyoxylate cycle, tricarboxylic acid cycle, and oxidative respiratory chain; and induces lipid peroxidation in the cytoplasm, leading to bacterial cuproptosis-like death. In this study, CuGA-VAN was cleverly designed to trigger a cascade reaction of targeting, drug release, ROS-catalyzed antibacterial activity and cuproptosis-like death. This provides an innovative idea for multidrug-resistant infections.
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Skin is the largest organ in the human body, and it is also the most important natural barrier. However, some accidents can cause skin damage. Bacterial infections and inflammatory reactions can hinder wound healing. Therefore, eliminating bacterial infections and regulating oxidative stress are essential. The use of antibiotics is no longer sufficient because of bacterial resistance. The development of new nanomaterials provides another way of thinking about bacterial drug resistance. In this study, bismuth selenide is modified with polyethylpyrrolidone to obtain a 2D nanomaterial with negligible toxicity and then added to a sodium polyacrylate hydrogel, which is nontoxic and has strong tissue adhesion and a weak antibacterial effect. To further enhance antibacterial performance, photothermal therapy is a good strategy. Under near-infrared light, Bi2Se3/PAAS shows a strong bactericidal effect. Bi2Se3/PAAS hydrogels also have certain antioxidant effects and are used to remove excess free radicals from wound infections. The effective therapeutic effect of Bi2Se3/PAAS/NIR on methicillin-resistant Staphylococcus aureus (MRSA) infection is further verified in animal models. Transcriptome analysis reveals that the Bi2Se3/PAAS hydrogel improves the function of vascular endothelial cells, regulates glucose and lipid metabolism, and promotes the healing of infected wounds.
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Emerging mycotoxins enniatins (ENNs) and beauvericin (BEA) pose potential health risks to humans through dietary exposure. However, research into their mechanisms of toxicity is limited, with a lack of comprehensive toxicological data. This study investigates from a hepatic lipid metabolism perspective, establishing a more precise and reliable 3D HepaRG hepatocyte spheroid model as an alternative for toxicity assessment. Utilizing physiological indices, histopathological analyses, lipidomics, and molecular docking techniques, it comprehensively elucidates the effects of ENNs and BEA on hepatic lipid homeostasis and their molecular toxicological mechanisms. Our findings indicate that ENNs and BEA impact cellular viability and biochemical functions, significantly altering lipid metabolism pathways, particularly those involving glycerophospholipids and sphingolipids. Molecular docking has demonstrated strong binding affinity of ENNs and BEA with key enzymes in lipid metabolism such as Peroxisome Proliferator-Activated Receptor α (PPARα) and Cytosolic Phospholipase A2 (cPLA2), revealing the mechanistic basis for their hepatotoxic effects and potential to impair liver function and human health. These insights enhance our understanding of the potential hepatotoxicity of such fungal toxins and lay a foundation for the assessment of their health risks.
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Plant non-structural carbohydrates (NSCs), which largely comprise starch and soluble sugars, are essential energy reserves to support plant growth and physiological functions. While it is known that increasing global deposition of nitrogen (N) affects plant concentration of NSCs, quantification of seasonal responses and drivers of woody species leaf and root NSCs to N addition at larger spatial scales remains lacking. Here, we systematically analyzed data from 53 field experiments distributed across China, comprising 1202 observations, to test for effects of N addition on woody plant leaf and root NSCs across and within growing and non-growing seasons. We found (1) no overall effects of N addition on the concentrations of leaf and root NSCs, soluble sugars or starch during the growing season or the non-growing season for leaves. However, N addition decreased root NSC and starch concentrations by 13.8 % and 39.0 %, respectively, and increased soluble sugars concentration by 15.0 % during the non-growing season. (2) Shifts in leaf NSC concentration under N addition were driven by responses by soluble sugars in both seasons, while shifts in root NSC were driven by soluble sugars in the non-growing season and starch and soluble sugars in the growing season. (3) Relationships between N, carbon, and phosphorus stoichiometry with leaf and root NSCs indicated effects of N addition on woody plant NSCs allocation through impacts on plant photosynthesis, respiration, and growth. (4) Effects of N addition on leaf and root NSCs varied with plant functional types, where effects were more pronounced in roots than in leaves during the non-growing season. Overall, our results reveal divergent responses of woody plant leaf and root NSCs to N addition within non-growing season and highlight the role of ecological stoichiometry and plant functional types in woody plant allocation patterns of NSCs in response to ongoing N deposition under global change.
Subject(s)
Nitrogen , Plant Leaves , Plant Roots , Seasons , China , Carbohydrates/analysis , Carbohydrate MetabolismABSTRACT
Background: This study investigates the link between genetic variants associated with kidney function and immunoglobulin A (IgA) nephropathy (IgAN) progression. Methods: We recruited 961 biopsy-proven IgAN patients and 651 non-IgAN end-stage renal disease (ESRD) patients from Ruijin Hospital. Clinical and renal pathological data were collected. The primary outcome was the time to ESRD. A healthy population was defined as estimated glomerular filtration rate >60 mL/min/1.73 m2 without albuminuria or hematuria. Fifteen single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of kidney function and genotyped by the SNaPshot. Immunohistochemistry in renal tissue and ELISA in urine samples were performed to explore the potential functions of genetic variations. Results: The rs77924615-G was independently associated with an increased risk for ESRD in IgAN patients after adjustments for clinical and pathologic indices, and treatment (adjusted hazard ratio 2.10; 95% confidence interval 1.14-3.88). No significant differences in ESRD-free survival time were found among different genotypes in non-IgAN ESRD patients (log-rank, P = .480). Moreover, rs77924615 exhibited allele-specific enhancer activity by dual-luciferase reporter assay. Accordingly, the urinary uromodulin-creatinine ratio (uUCR) was significantly higher in healthy individuals with rs77924615 AG or GG than in individuals with AA. Furthermore, uromodulin expression in tubular epithelial cells was higher in patients with rs77924615 AG or GG. Finally, we confirmed that an increased uUCR (P = .009) was associated with faster IgAN progression. Conclusion: The SNP rs77924615, which modulates the enhancer activity of the UMOD gene, is associated with renal function deterioration in IgAN patients by increasing uromodulin levels in both the renal tubular epithelium and urine.
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Non-Abelian holonomy, a noncommutative process that measures the parallel transport of non-Abelian gauge fields, has so far been realized in degenerate Hermitian systems with degenerate eigenstates or nondegenerate non-Hermitian systems with exceptional points. Here, we introduce non-Abelian holonomy into degenerate non-Hermitian systems possessing degenerate exceptional points and degenerate energy topologies. The interplay between energy degeneracy and energy topology around exceptional points leads to a non-Abelian holonomy with multiple energy levels and multiple degenerate levels simultaneously, going beyond that in degenerate Hermitian systems with a single energy level, or in nondegenerate non-Hermitian systems with a single degenerate level. We exploit an on-chip photonic platform to experimentally demonstrate the holonomy induced non-Abelian phenomenon, including the switching of eigenstates associated with different degenerate exceptional points and sequence-dependent holonomic outcomes. Our work shifts the paradigm of non-Abelian holonomy and adds new degrees of freedom for non-Abelian applications.
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Adenoid hypertrophy can lead to adenoidal mouth breathing, which can result in "adenoid face" and, in severe cases, can even lead to respiratory tract obstruction. The Fujioka ratio method, which calculates the ratio of adenoid (A) to nasopharyngeal (N) space in an adenoidal-cephalogram (A/N), is a well-recognized and effective technique for detecting adenoid hypertrophy. However, this process is time-consuming and relies on personal experience, so a fully automated and standardized method needs to be designed. Most of the current deep learning-based methods for automatic diagnosis of adenoids are CNN-based methods, which are more sensitive to features similar to adenoids in lateral views and can affect the final localization results. In this study, we designed a local attention-based method for automatic diagnosis of adenoids, which takes AdeBlock as the basic module, fuses the spatial and channel information of adenoids through two-branch local attention computation, and combines the downsampling method without losing spatial information. Our method achieved mean squared error (MSE) 0.0023, mean radial error (MRE) 1.91, and SD (standard deviation) 7.64 on the three hospital datasets, outperforming other comparative methods.
Subject(s)
Adenoids , Hypertrophy , Adenoids/pathology , Adenoids/diagnostic imaging , Humans , Child , Male , Female , Deep Learning , Child, Preschool , Cephalometry/methodsABSTRACT
BACKGROUND: Studies have found that the use of clinically approved caffeine and modafinil can alleviate cognitive impairment due to sleep deprivation (SD) to some extent. However, the neural mechanisms by which these two cognitive enhancers work to counteract the effects of SD on cognitive impairment remain unclear. METHODS: A double-blind within-subjects experiment using resting-state functional magnetic resonance imaging (rs-fMRI) was designed. Participants underwent three 36-h SD trials, each of which involved taking 200 mg of caffeine, modafinil, or placebo at the 28th and 32 nd h of SD. Sixteen subregions of the thalamus were selected as the regions of interest and changes in functional connectivity (FC) between the thalamus and the other brain regions were explored after the participants took caffeine or modafinil. RESULTS: The subjective sleepiness of the participants increased with the duration of SD. compared with placebo, modafinil and caffeine had insignificant effects on wakefulness or sleepiness. However, in terms of neural FC, we found varying degrees of attenuation or enhancement of the FC between the thalamus and other regions. Taking caffeine during SD weakened the FC between the right rostral temporal thalamus (rTtha) subregion and the left lingual gyrus compared with placebo. Caffeine enhanced the FC between three subregions of the thalamus, namely the left sensory thalamus, the left rTtha, and the right lateral pre-frontal thalamus, and the right inferior temporal, left orbitofrontal, and right superior occipital gyris. Modafinil weakened the FC between the right posterior parietal thalamus and left middle temporal gyrus, and enhanced the FC between the left medial pre-frontal thalamus, left rTtha, and right occipital thalamus and left middle frontal gyrus. CONCLUSIONS: After 36 h of total SD, modafinil and caffeine administration enhanced or attenuated the time-domain correlations between various subregions of the thalamus and brain regions of the frontal and temporal lobes in healthy adults, compared with placebo. These results provide valuable evidence for further unraveling the neuropharmacological mechanisms of caffeine and modafinil, as well as important insights for exploring effective pharmacological intervention strategies against SD.
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Purpose: Chlamydia trachomatis (C. trachomatis) is associated with several gynecological tumors; yet its prognostic role in breast cancer remains unclear. Thus, we investigated the prognostic role of anti-C. trachomatis immunoglobulin G (IgG) in breast cancer patients and the modification effects of pro-inflammatory cytokines. Methods: The serum levels of C. trachomatis IgG and four pro-inflammatory cytokines were measured. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), including product terms to assess the modification effects of pro-inflammatory cytokines on the association between C. trachomatis IgG and breast cancer prognosis. Results: From 2008 to 2018, 1121 breast cancer patients were recruited and followed up until December 31, 2021, with a median follow-up time of 63.91 months (interquartile range: 39.16-90.08 months). Patients positive for C. trachomatis IgG showed HRs of 1.09 (95% CI, 0.67-1.78) for overall survival (OS) and 1.24 (0.87-1.78) for progression-free survival (PFS), compared to those who were negative. These associations became statistically significant in women aged 50 years or younger (HR=1.43, 95% CI=0.79-2.58 for OS; HR=1.79, 95% CI=1.16-2.77 for PFS). Positive C. trachomatis IgG serology was associated with adverse prognostic effects among patients with higher levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-1ß), but with favorable prognostic effects for those with low levels. These interactions were particularly significant in those aged 50 years or younger. Conclusion: In breast cancer patients younger than 50 years of age or with higher levels of pro-inflammatory cytokines, C. trachomatis infection appeared to have a negative prognostic impact. These findings highlight the significance of C. trachomatis in predicting prognosis and personalized therapy for breast cancer patients.
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Acute promyelocytic leukemia (APL), a distinctive subtype of acute myeloid leukemia (AML), is characterized by the t(15; 17) translocation forming the PML-RARα fusion protein. Recent studies have revealed a crucial role of retinoid X receptor α (RXRα) in PML-RARα's tumorigenesis. This necessitates the development of dual RARα and RXRα targeting compounds for treating APL. Here, we developed a pair of brominated retinoid isomers, 5a and 5b, exhibiting RARα agonistic selectivity among the RAR subtypes and RXRα partial agonistic activities. In the treatment of APL cells, low doses (RARα activation range) of 5a and 5b degrade PML-RARα and strongly induce differentiation, while higher doses (RXRα activation range) induce G2/M arrest and apoptosis in both all-trans retinoic acid (ATRA)-sensitive and resistant cells. We replaced the bromine in 5a with chlorine or iodine to obtain compounds 7 or 8a. Interestingly, the chlorinated compound 7 tends to activate RXRα and induce G2/M arrest and apoptosis, while the iodinated compound 8a tends to activate RARα and induce differentiation. Together, our work underscores several advantages and characteristics of halogens in the rational design of RARα and RXRα ligands, offering three promising drug candidates for treating both ATRA-sensitive and resistant APL.
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Microbial carbon utilization efficiency (CUE) is a crucial indicator for evaluating the efficiency of soil carbon sequestration and transformation, which is applied to quantify the proportion of soil carbon extracted by microbes for anabolism (growth) and catabolism (respiration). Previous studies have shown that the degradation of Moso bamboo forests (Phyllostachys edulis) destroyed the aboveground bamboo structure, reduced vegetation carbon storage, and weakened ecosystem carbon sequestration capacity. Interestingly, soil organic carbon stocks are gradually increasing. However, the mechanism by which degradation-induced changes in soil and vegetation characteristics affect microbial CUE and drive soil carbon sequestration remains unclear. Here we selected four stands with the same origin but different degradation years (intensive management, CK; 2 years' degradation, DM1; 6 years' degradation, DM2; and 10 years' degradation, DM3) based on the local management profiles. The principle of space-for-time substitution was used to investigate the changes in microbial CUE along a degradation time and to further identify the controlling biotic and abiotic factors. Our finding showed that microbial CUE increased by 12.27 %, 31.01 %, and 55.95 %, respectively, compared with CK; whereas microbial biomass turnover time decreased from 23.99 ± 1.11 to 17.16 ± 1.20 days. Promoting microbial growth was the main pathway to enhance microbial CUE. Massive inputs of vegetative carbon replenished soil carbon substrate content, and altered microbial communities and life history strategy, which in turn promoted microbial growth and increased microbial CUE. These findings provide theoretical support for the interactions between carbon dynamics and microbial physiology in degraded bamboo forests, and reinforce the importance of vegetation and microbial properties and soil carbon substrates in predicting microbial CUE.
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BACKGROUND: Rifampicin resistant tuberculosis (RR-TB) poses a growing threat to individuals and communities. This study utilized a seasonal autoregressive integrated moving average (SARIMA) model to quantitatively predict the monthly incidence of RR-TB in Yunnan Province which could guide government health administration departments and the centers for disease control and prevention (CDC) in preventing and controlling the RR-TB epidemic. METHODS: The study utilized routine surveillance reporting data from the infectious Disease Network Surveillance and Reporting System. Monthly incidence rates of RR-TB were collected from January 2019 to December 2022. A time series SARIMA model was used to predict the number of monthly RR-TB cases in Yunnan Province in 2023, and the model was validated using time series plots, seasonal and non-seasonal differencing, autocorrelation and partial autocorrelation analysis, and white noise tests. RESULTS: From 2019 to 2022, the incidence of RR-TB decreases as the incidence of all TB decreases (P < 0.05). There was no significant change in the proportion of RR-TB among all TB cases, which remained within 2.5% (P>0.05). The time series decomposition shows that it presented obvious seasonality, periodicity and randomness after being decomposed. Time series analysis was performed on the original series after 1 non-seasonal difference and 1 seasonal difference, the ADF test showed P < 0.05. According to ACF and PACF, the SARIMA (1, 1, 1) (1, 1, 0)12 model was chosen and statistically significant model parameter estimates (P < 0.05). The predicted seasonal trend of RR-TB incidence in 2019 to 2023 was similar to the actual data. The percentage accuracy in the prediction excesses 80% in 2019 to 2022 and is all within 95% CI. However there was a certain gap between the actual incidence and the predicted value in 2023, and the acutual incidence had increased by 12.4% compared to 2022. The percentage of accuracy in the prediction was only 70% in 2023. CONCLUSIONS: We found the incidence of RR-TB was based on that of all TB in Yunnan. The SARIMA model successfully predicted the seasonal incidence trend of RR-TB in Yunnan Province in 2019 to 2023, but the prediction precision could be influenced by factors such as new infectious disease outbreaks or pandemics, social issues, environmental challenges or other unknown risks. Hence CDCs should pay special attention to the post epidemic effects of new infectious disease outbreaks or pandemics, carry out monitoring and early warning, and better optimize disease prediction models.
Subject(s)
Rifampin , Seasons , Tuberculosis, Multidrug-Resistant , China/epidemiology , Humans , Incidence , Rifampin/therapeutic use , Tuberculosis, Multidrug-Resistant/epidemiology , Models, StatisticalABSTRACT
BACKGROUND: Rapid proliferation is a hallmark of glioblastoma multiforme (GBM) and a major contributor to its recurrence. Aberrant ubiquitination has been implicated in various diseases, including cancer. In our preliminary studies, we identified Ubiquitin-conjugating enzyme E2S (UBE2S) as a potential glioma biomarker, exhibiting close associations with glioma grade and protein phosphatase 1, regulatory subunit 105 (Ki67) expression levels. However, the underlying molecular mechanisms remained elusive. NF-κB is an important signaling pathway that promotes GBM proliferation. Direct intervention targeting NF-κB has not yielded the expected results, prompting the exploration of new molecules for regulating NF-κB as a new direction. METHODS: This study employed methods including yeast two-hybrid and immunoprecipitation to uncover the interaction between UBE2S and A kinase interacting protein 1 (AKIP1). Laser confocal microscopy was used to observe the localization of UBE2S and AKIP1. Dual luciferase reporter genes were utilized to observe the activation of NF-κB. RESULTS: Our findings demonstrate that UBE2S deficiency significantly impedes GBM progression, both in vitro and in vivo. Mechanistically, UBE2S plays a crucial role in recruiting Ubiquitin Specific Peptidase 15 (USP15), facilitating the removal of K11-linked ubiquitination on AKIP1. This action enhances AKIP1 stability within the GBM context. The resulting increase in AKIP1 levels further augments nuclear factor kappa-B (NF-κB) transcriptional activity, leading to the upregulation of downstream genes regulated by the NF-κB pathway, thereby promoting GBM progression. CONCLUSIONS: In summary, our findings reveal the role of the UBE2S/AKIP1-NF-κB axis in regulating GBM progression and provide novel evidence supporting UBE2S as a potential drug target for GBM.
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PM2.5 pollution has been associated with the incidence of lung cancer, but the underlying mechanism is still unclear. PIWI-interacting RNAs (piRNAs), initially identified in germline cells, have emerged as a novel class of small non-coding RNAs (26 - 32 nucleotides) with diverse functions in various diseases, including cancer. However, the role and mechanism of piRNAs in the development of PM2.5-induced lung cancer remain to be clarified. In the presented study, we used a PM2.5-induced malignant transformation cell model to analyze the change of piRNA profiles. Among the disturbed piRNAs, piR-27222 was identified as an oncogene that inhibited cell death in a m6A-dependent manner. Mechanistically, we found that piR-27222 could deubiquitinate and stabilize eIF4B by directly binding to eIF4B and reducing its interaction with PARK2. The enhanced expression of eIF4B, in turn, promoted the expression of WTAP, leading to increased m6A modification in the Casp8 transcript. Consequently, the stability of Casp8 transcripts was reduced, rendering lung cancer cells resistant to PANoptosis. Collectively, our findings reveal that PM2.5 exposure up-regulated piR-27222 expression, which could affect EIF4B/WTAP/m6A axis, thereby inhibiting PANoptosis of cells and promoting lung cancer. Our study provides new insights into understanding the epigenetic mechanisms underlining PM2.5-induced lung cancer.